Human Immunoglobulin G and Immunoglobulin G Subclasses: Biochemical, Genetic, and Clinical Aspects

Abstract

Human IgG consists of two identical heavy (H) chains and two identical light (L) chains joined by interchain disulfide bridges. Heterogeneity in the amino acid sequences of the H and L polypeptides results in at least three types of IgG variants at the structural and genetic levels. The four isotypic forms are IgG1, IgG2, IgG3, and IgG4, which share extensive homologies in the primary structure of their H chains. As a result, the subclasses cross-react antigenically, but they can be differentiated on the basis of subtle architectural dissimilarities. The biological and effector properties of the IgG isotypes have been associated, in part, with their structural differences. Genes determining the synthesis of human IgG heavy chains are located on chromosome 14. In several clinical situations the isotypes appear to be regulated or expressed in patterns reflecting the gene arrangement. The numeric designations of the subclasses correspond to the order of their proportional amounts in healthy adult serum: IgGl> IgG2 > IgG3 > IgG4. Awareness of the importance of the roles of the four IgG isotypes in human health has steadily increased since they were first described in the 1960s. The recognition that deficits or increases in selected IgG subclasses may have clinical consequences has prompted considerable interest in quantifying the four isotypes in clinical specimens. In particular, deficiencies of IgG2, IgG3, and IgG4, singly or combined, are associated with chronic infections which may not be readily recognized in otherwise healthy people with normal serum total IgG concentrations. Different assay methods using polyclonal or monoclonal antisera with various calibrants have been applied; however, no standardized method exists at the present. IgG deficits are associated with gene defects and are acquired in secondary immunodeficiencies in conjunction with other disorders. IgG isotype selectivity has been recognized in autoimmune diseases and in response to carbohydrate and protein antigens derived from pathogenic microorganisms and ommon allergens.